The heavy metal cadmium, a known environmental pollutant, has been implicated as a causative agent in the development of lung pathology. It has been suggested that one of the sites of cadmium toxicity is the oxidative metabolism of the pulmonary alveolar macrophage. At present, there is little known about the interaction of cadmium with the alveolar macrophage under physiological conditions. It is the purpose of the proposed research, therefore, to study the transport, intracellular distribution, and accumulation of cadmium by the pulmonary alveolar macrophage and to relate the amount of cadmium accumulated within the cells to alterations in physiological function. Transport by macrophage monolayers will be quantitated by the use of cadmium109. The intracellular distribution of cadmium will be determined by measuring the radioactivity present in the sub-cellular fractions (i.e., soluble cytoplasmic fraction, mitochondria, microsomes, and membranes) obtained after cell homogenation and differential centrifugation. Attempts to identify a specific cadmium-binding protein will be made by using column chromatographic techniques. Direct measurements of the cadmium content of macrophages will be made with the use of an atomic absorption spectrophotometer equipped with a micro-atomizer. Experiments will then be conducted to determine how the rate of cadmium transport is affected by pH, divalent ions, thiol-containing agents, protein(s) and alveolar lining material, and to determine whether cadmium accumulation can occur during the phagocytosis of bacteria and/or kaolin. Macrophages that have accumulated known amounts of cadmium under different environmental conditions will also be monitored for phagocytic activity, release of lysosomal enzymes, endogenous respiration, and ATPase activity. Comparative studies with macrophages from various animal sources are planned. It is hoped that the results of the proposed study will contribute to our understanding of the role cadmium plays in the development of lung pathology in man.